Suppression of microRNA-155 exerts an anti-inflammatory effect on CD4+ T cell-mediated inflammatory response in the pathogenesis of atherosclerosis

• 作者: Chen Liu Jiayu Zheng Jinqiang Shen Shouguo Yang Tao Hong Wenshuo Wang
• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: coronary atherosclerosis miR-155 inflammatory response NF-κB
• 年，卷（期）: 2020,（6）
• 页码范围: 654-664
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/abbs/gmaa040

摘要

In the current study,we aimed to investigate the effects of miR-155 on CD4+ T cell-mediated immune response in the pathogenesis of atherosclerosis.CD34+ hematopoietic stem cells,CD4+ T lymphocytes,endothelial cells (ECs),and vascular smooth muscle cells (VSMCs) were harvested from the same donor.Knockdown of miR-155 in the CD4+ T cells was achieved by lentiviral transfection,whereas control RNA-transfected or untransfected lymphocytes were used as controls.The transfected CD4+ T cells were activated by incubating with oxidized low-density lipoprotein-treated dendritic cells.The proliferative capacities,phenotype distribution,and cytokine secretion profiles of the activated CD4+ T cells from different groups were evaluated.The activated lymphocytes were used to treat ECs co-cultivated with VSMCs.The ability of the CD4+ T cells to induce the apoptosis of the ECs and to promote the proliferation of the VSMCs was investigated.Inhibition of miR-155 was found to significantly reduce the proliferation rate of the transfected CD4+ T cells.CD4+ T lymphocytes transfected with the miR-155 inhibitor showed increased populations of T helper type 2 and regulatory T cells,as well as more production of anti-inflammatory cytokines.MiR-155 knockdown was also shown to significantly hamper the ability to CD4+ T cells to induce EC apoptosis and to promote the growth of VSMCs.Our data suggested that inhibition of miR-155 in CD4+ T cells could slow down the formation of atherosclerotic plaques.These results lay the groundwork for future research on the therapeutic potential of miR-155 against atherosclerosisassociated cardiovascular diseases.